standardized-identification-compound-structure-tibetan-medicine-using

Standardized Identification of Compound Structure in Tibetan Medicine Using Ion Trap Mass Spectrometry and Multiple-Stage Fragmentation Analysis

Tibetan medicines are complex and contain numerous unknown compounds, making in-depth research on their molecular structures crucial. Liquid ...

using-an-vitro-tissue-perfusion-system-to-detect-functional

Using An In Vitro Tissue Perfusion System to Detect the Functional Activities of Isolated Intestinal Tubes in Real Time

Gastrointestinal diseases, which have a high incidence, pose considerable challenges for humans. The small intestine is integral to food and drug ...

Chengdu University of Traditional Chinese Medicine

To explore the scientific connotation of the discrepant pharmaceutical activities between the head and tail of Angelica sinensis diels (AS), an important herb extensively utilized in Chinese medicine, by the approach of transcriptome sequencing.

Differentially expressed genes in heads and tails of Angelica sinensis diels: Focusing on ferulic acid metabolism.

To assess a new and highly specific, but low-cost, easily performed and suitable for large-scale applications method for renal fibrosis (RF) diagnostics.

A PEG-based method for the isolation of urinary exosomes and its application in renal fibrosis diagnostics using cargo miR-29c and miR-21 analysis.

Recently, gut flora has been linked to the onset of obesity and has been shown to influence the host's metabolism. Acupuncture is a well-known agent used for the treatment of numerous diseases such as obesity. This study aimed to explore the impacts of electroacupuncture treatment on gut microbiota composition and function in obese mice. Pyrosequencing of 16S rRNA genes and Metagenomic analysis of the fecal microbiota were used for this purpose. The basic parameters of body weight, Lee's index, serum lipid and epididymal adipose weight were ameliorated significantly after introducing an electroacupuncture intervention. Acidobacteria, Cyanobacteria and Basidiomycota (Normal group) and Fusobacteria, Firmicutes and Spirochmycetes (Model group) were remarkably affluent at the phylum level. Bacteroides sp. CAG: 927 and Prevotella sp. CAG: 1031 (Normal group), Lachnospiraceae bacterium and Helicobacter rodentium (Model group) at the species level were distinctly enriched. The structures and functions of the intestinal flora were significantly different between healthy and obese mice, and animals in the acupuncture group gradually tended towards healthy controls. Moreover, electroacupuncture altered the bacterial diversity and metabolic genes to establish new balance, observed the obvious change from 7[Formula: see text]d and stabilized gradually through 21[Formula: see text]d. These findings suggested gut flora could be a novel target of electroacupuncture treatment against obesity.

Regulating Gut Flora Dysbiosis in Obese Mice by Electroacupuncture.

Obesity is one of the most serious public health challenges in the world. Obesity during early life has been associated with an increased risk of neurodevelopmental disorders, including deficits in learning and memory, yet the underlying mechanisms remain unclear. Here, we show that early life high-fat diet (HFD) feeding impairs hippocampus-dependent contextual/spatial learning and memory, and alters the gut microbiota, particularly by depleting Akkermansia muciniphila (A. muciniphila), in mice. Transplantation of the HFD microbiota confers hippocampus-dependent learning and memory deficits to mice fed a chow diet. Oral treatment of HFD-fed mice with the gut commensal A. muciniphila corrects gut permeability, reduces hippocampal microgliosis and proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6) expression, and restores neuronal development and synapse plasticity, thus ameliorates defects in learning and memory. Interestingly, treatment of mice with lipopolysaccharide (LPS) mimics HFD-induced hippocampus-dependent cognitive impairment in chow-fed mice. In line with these findings, pharmacologic blockade of Toll-like receptor 4 (TLR4) signalling or antibiotics treatment both effectively prevent hippocampus-dependent learning and memory deficits in HFD-fed mice. Collectively, our findings demonstrate an unexpected pivotal role of gut microbiota in HFD-induced cognitive deficits and identify a potential probiotic therapy for obesity associated with cognitive dysfunction during early life.

Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila.

The prefrontal cortex (PFC) plays an important role in regulating anxiety-like phenotypes and social behaviors, and impairments in this brain region has been linked to social deficits in mammals. Childhood obesity is associated with an increased risk of neuropsychiatric behavioral abnormalities, including attenuated social preference and increased anxiety-like behaviors in adulthood. However, little data are available on the impact of obesity during adolescence on PFC-dependent behaviors. Herein, we use the mice pups to illuminate whether and how high-fat diet (HFD) feeding in adolescence affects medial prefrontal cortex (mPFC)-dependent behaviors, and what the underlying cellular and molecular mechanism is. We found that juvenile HFD feeding results in the accumulation of senescent astrocytes and microglia in the mPFC of mice. Furthermore, we found a causal link between the accumulation of senescent glial cells and HFD-induced neuropsychiatric behavioral abnormalities. Pharmacological clearance of senescent glial cells in HFD-fed mice enhances neuronal activity and reserves synaptic excitatory/inhibitory balance, thus preserving normal behaviors. Collectively, these results show that senescent glial cells play a significant role in the initiation and progression of juvenile obesity-mediated neuropsychiatric behavioral abnormalities, and suggest that targeting senescent glial cells may provide a therapeutic avenue for the treatment of obesity-related neuropsychiatric disorders in children.

Juvenile high-fat diet-induced senescent glial cells in the medial prefrontal cortex drives neuropsychiatric behavioral abnormalities in mice.

Social experiences during early life are thought to be critical for proper social and emotional development. Conversely, social insults during development causes long-lasting behavioral abnormalities later in life. However, how juvenile social deprivation influences social and emotional behaviors remains poorly understood. Here, we show that juvenile social isolation induces a shift in microbial ecology that negatively impacts social and emotional behaviors in adulthood. These behavioral changes, which occur during this critical period are transferable to antibiotic pre-treated mice by fecal microbiota transplant. In addition, juvenile social isolation decreases the expression of oxytocin receptor (OXTR) in the medial prefrontal cortex (mPFC), and increases the amounts of fecal propionic acid (PA), a short-chain fatty acid derived from gut micobiota. Accordingly, infusion with an OXTR antagonist (OXTR-A, l-368,899) specifically in the mPFC or supplementation of PA both can cause social deficits and anxiety-like behaviors in group housed mice. Collectively, our findings reveal that juvenile social experience regulates prefrontal cortical OXTR expression through gut microbiota-produced PA and that is essential for normal social and emotional behaviors, thus providing a cellular and molecular context to understand the consequences of juvenile social deprivation.

Commensal microbe-derived propionic acid mediates juvenile social isolation-induced social deficits and anxiety-like behaviors.

Neuropsychiatric dysfunction and reactive microglia are hallmarks of high-fat diet (HFD)-induced obesity, yet whether these reactive microglia contribute to HFD-induced obesity-related behavioral abnormalities and the underlying mechanisms remain unclear. Here, we show that HFD feeding causes social deficits and anxiety-like behaviors with impaired neuronal activity and alters the gut microbiota, particularly by depleting Lactobacillus reuteri (L. reuteri), in mice. The profiles of microbiome and metabolome in HFD-fed mice predict that specific microbial taxa and their metabolites regulate HFD-induced obesity-related behavioral abnormalities. Oral treatment with the L. reuteri reduces microglial activation and increases dendritic spine density, thus ameliorates social deficits and anxiety in HFD-fed mice. HFD-fed mice that are administered L. reuteri are also found to accumulate butyrate in their gut, sera and brain. Moreover, supplementation of butyrate improves behavioral abnormalities and modulates microglial homeostasis in HFD-fed mice. In addition, selectively removal of microglia through a pharmacologic approach can rescue dendritic spine loss and increase neuronal activity that profoundly alleviates social deficits and anxiety arising from HFD-induced obesity. Overall, this study reveals an unexpected pivotal role of gut commensal-derived butyrate in HFD-induced social deficits and anxiety-like behaviors through regulation of microglial homeostasis and identifies a potential probiotic treatment for HFD-induced obesity-related behavioral abnormalities.

Gut commensal-derived butyrate reverses obesity-induced social deficits and anxiety-like behaviors via regulation of microglial homeostasis.

Obesity, a growing health problem in the world, is related to a series of mental disorders, including anxiety and depression. XiaoYao San (XYS), a prescription of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of anxiety and depression in China. However, the efficacy of XYS on obesity-related neuropsychiatric dysfunction and the underlying neural mechanisms remain unclear. Here, using a high-fat diet (HFD)-induced obese model, we found that XYS treatment significantly improves obesity-related anxiety- and depression-like behaviors and alters the gut microbiome, particularly by increasing the relative abundance of Faecalibaculum rodentium (F. rodentium), in mice. Interestingly, selective supplementation with F. rodentium or its metabolic products, short-chain fatty acids (SCFAs), is sufficient to rescue anxiety- and depression-like behaviors in HFD-fed mice. Next, we determined that the transcriptional level of dopamine D2 receptor (DRD2), which activation usually inhibits inflammation in the central nervous system (CNS), is significantly increased in the medial prefrontal cortex (mPFC) of XYS-treated mice when compared with that of vehicle-treated controls. Moreover, enriched pathways analysis with the differential expression genes (DEGs) showed that some of these DEGs are enriched in neuroinflammatory pathways. We further noticed that treatment with XYS contributes to controlling microglial activation and proinflammatory responses in the mPFC and hippocampus of HFD-fed mice. Overall, this study reveals that XYS rescues HFD-induced anxiety and depression via modulating gut microbiota-derived metabolites and that XYS is a potential therapeutic strategy for treating obesity-associated mental disorders.

Xiaoyao San ameliorates high-fat diet-induced anxiety and depression via regulating gut microbiota in mice.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the  interactions of SJZD and IBS-D's intestinal microbiota.

Cocultivation of Chinese prescription and intestine microbiota: SJZD alleviated the major symptoms of IBS-D subjects by tuning neurotransmitter metabolism.

Lack of maternal care and attention during infancy and childhood increases the likelihood of developing a range of neuropsychiatric disorders, such as social deficits, working memory impairment, and anxiety-like behaviors, in adulthood. However, the neuroregulatory signaling through which early-life stress causes behavioral and cognitive abnormalities in the offspring is largely unexplored. Here, we show that in mice, unpredictable maternal separation (MS) during the early postnatal period impairs neuronal development in the medial prefrontal cortex (mPFC) and results in long-lasting behavioral changes. Additionally, MS disrupts excitatory neurotransmission and inhibits the neuronal activity of pyramidal neurons in the mPFC. Differentially expressed gene (DEG) analysis of RNA sequencing (RNA-seq) data of mPFC showed that dopamine D1 receptor (D1R) was significantly downregulated in MS animals. Finally, we show that pharmacological activation of D1R signaling specifically in the mPFC improves neuronal excitability and rescues behavioral and cognitive dysfunction of MS mice, whereas pharmacologically inhibiting of D1R in the mPFC mimics MS-induced behavioral abnormalities in control mice. Together, our results identify D1R signaling in the mPFC, at least in part, as a potential therapeutic target for the behavioral and cognitive abnormalities caused by deprivation of maternal care in early life.

Activation of D1R signaling in the medial prefrontal cortex rescues maternal separation-induced behavioral deficits through restoration of excitatory neurotransmission.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-, IL-1, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Maternal immune activation (MIA) resulting from viral infections during pregnancy is linked to increased rates of neurodevelopmental disorders in offspring. However, the mechanisms underlying MIA-induced neurobehavioral abnormalities remain unclear. Here, we used a poly (I:C)-induced MIA mouse model to demonstrate the presence of multiple behavioral deficits in male offspring. Through RNA sequencing (RNA-seq), we identified significant upregulation of genes involved in axonogenesis, synaptogenesis, and glutamatergic synaptic neurotransmission in the mPFC of MIA mice. Electrophysiological analyses further revealed an excitatory-inhibitory (E/I) synaptic imbalance in mPFC pyramidal neurons, leading to hyperactivity in this brain region. Cannabidiol (CBD) effectively alleviated the behavioral abnormalities observed in MIA offspring by reducing glutamatergic transmission and enhancing GABAergic neurotransmission of mPFC pyramidal neurons. Activation of GPR55 by lipid lysophosphatidylinositol (LPI), an endogenous GPR55 agonist, specifically in the mPFC of healthy animals led to MIA-associated behavioral phenotypes, which CBD could effectively reverse. Moreover, we found that a GPR55 antagonist can mimic CBD's beneficial effects, indicating that CBD's therapeutic effects are mediated via the LPI-GPR55 signaling pathway. Therefore, we identified mPFC as a primary node of a neural network that mediates MIA-induced behavioral abnormalities in offspring. Our work provides insights into the mechanisms underlying the developmental consequences of MIA and identifies CBD as a promising therapeutic approach to alleviate these effects.

Restoring prefrontal cortical excitation-inhibition balance with cannabidiol ameliorates neurobehavioral abnormalities in a mouse model of neurodevelopmental disorders.

ArticleTotal : 2	Year
Publication title	2023
Publication title	2024

Article	Year
Differentially expressed genes in heads and tails of Angelica sinensis diels: Focusing on ferulic acid metabolism. Chinese journal of integrative medicine\| PubMed ID: 27586474	2017
A PEG-based method for the isolation of urinary exosomes and its application in renal fibrosis diagnostics using cargo miR-29c and miR-21 analysis. International urology and nephrology\| PubMed ID: 29330775	2018
Regulating Gut Flora Dysbiosis in Obese Mice by Electroacupuncture. The American journal of Chinese medicine\| PubMed ID: 30284469	2018
Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology\| PubMed ID: 31207607	2019
Juvenile high-fat diet-induced senescent glial cells in the medial prefrontal cortex drives neuropsychiatric behavioral abnormalities in mice. Behavioural brain research\| PubMed ID: 32750465	2020
Commensal microbe-derived propionic acid mediates juvenile social isolation-induced social deficits and anxiety-like behaviors. Brain research bulletin\| PubMed ID: 33279588	2021
Gut commensal-derived butyrate reverses obesity-induced social deficits and anxiety-like behaviors via regulation of microglial homeostasis. European journal of pharmacology\| PubMed ID: 34270984	2021
Xiaoyao San ameliorates high-fat diet-induced anxiety and depression via regulating gut microbiota in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 36279723	2022
Cocultivation of Chinese prescription and intestine microbiota: SJZD alleviated the major symptoms of IBS-D subjects by tuning neurotransmitter metabolism. Frontiers in endocrinology\| PubMed ID: 36452327	2022
Activation of D1R signaling in the medial prefrontal cortex rescues maternal separation-induced behavioral deficits through restoration of excitatory neurotransmission. Behavioural brain research\| PubMed ID: 36627054	2023
Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation. Neural plasticity\| PubMed ID: 36910013	2023
Restoring prefrontal cortical excitation-inhibition balance with cannabidiol ameliorates neurobehavioral abnormalities in a mouse model of neurodevelopmental disorders. Neuropharmacology\| PubMed ID: 37716533	2023

Yili Wang

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